The acute response of colonic epithelial cells to 1,2-dimethylhydrazine delivered subcutaneously at a weekly dose level of 20 mg/kg body weight to CF1 mice has been shown to induce a permanent alteration in the distribution of the major zone of DNA synthesis within some crypts one week following the 5th treatment. This coincides with the time when areas of focal atypism of microscopic adenomas are found. This proposal using histologic, autoradiographic and enzymatic endpoints seeks to determine firstly if this response by colonic epithelial cells is elicited only by an organotropic carcinogen or if weekly injections of alkylating agents and antimetabolites such as cytoxan, bleomycin, 5-fluorouracil, hydroxyurea, and cytosine arabinoside induce similar alterations in cell proliferation. Secondly, mouse strains resistant to DMH (AKR/J, GR and DMA/2) will be examined and the acute effect of DMH on their colonic epithelial cells compared with that found in the sensitive CF1 strain. The effect of the ultimate carcinogen of DMH activation MAM on both DMH sensitive (SWR/J and P/J) and resistant strains will also be studied, as well as the effect of pyrazole administered prior to MAM. Lastly, substances such as selenium, zinc, beta sitosterol, lithocholic acid, deoxycholic acid, and vitamin C will be delivered prior to and during DMH and MAM treatment to determine if any modification of the acute reaction takes place and at which stage of the damage and repair cycle these dietary additives may operate.